Zinc ketone enolates synthesis

In the reaction of a simple ketone enolate with a chiral aldehyde, the use of a zinc enolate may offer advantages in terms of facial selectivity with respect to the use of a lithium enolate. This is exactly the result recorded in the condensation of the kinetic enolate of 2-undecanone 140 with 141, the key step in a total synthesis of (-l-)-preussin 142, a fermentation product with antifungal and antibacterial activity (equation 77)169. While 2-undecanone Li enolate did not display stereocontrol when added to 141, an acceptable syn diastereoselectivity was displayed by the Zn enolate 140. 

Scheme 5.109 Copper-catalyzed enantioselective conjugate addition of dimethyl zinc and enolate trapping by palladium-catalyzed allylic alkylation to ketone 427. Application to a synthesis of pumiliotoxin C.

They have developed direct asymmetric synthesis of quaternary carbon centers via addition-elimination process. The reactions of chiral nitroenamines with zinc enolates of a-substituted-8-lactones afford a,a-disubstituted-6-lactones with a high ee through addition-elimination process, in which (5)-(+)-2-(methoxy methy l)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as a-substituted ketones, esters, and amides has failed to yield high ee. 

Aldol condensation of the zinc enolate of resin-bound alkyl ester 29 with aromatic aldehyde or ketone forms a P-hydroxy ester, which upon treatment with DIBAL-H leads to simultaneous reduction and cleavage of the ester moiety from the resin to give a soluble 1,3-diol 31 [31], Parallel synthesis utilizing three ester and nine carbonyl building blocks afforded a library of 27 analogs which was screened for antioxidative efficiency using a ferric thiocyanate assay. 

However, we are not surprised that an enolate ion is formed from a ketone in basic solution. The oxyallyl cation is much more surprising. How can we be convinced that it really is an intermediate There are several alternative ways to make the same intermediate. If basic nucleophiles such as the methoxide ion are avoided and reaction of zinc with an a,a -dibromoketone in a nonnucleophilic solvent like diglyme is used instead, the oxyallyl cation can be trapped in a Diels-Alder reaction. This is tile basis for a good synthesis of seven-membered rings. 

---